1. Back to Basics Nephrology 2010 Major issues in Nephrology, Electrolytes, Acid-base disturbances

2. CKD

3. K/DOQI Classification of Chronic Kidney Disease StageGFR (≥3mo) Description (ml/min/1.73m 2 ) (ml/min/1.73m 2 ) 1  90 Damage with normal GFR 1  90 Damage with normal GFR 260-90 Mild  GFR 260-90 Mild  GFR 3 30-59 Moderate  GFR 3 30-59 Moderate  GFR 4 15-29 Severely  GFR 4 15-29 Severely  GFR 5 <15 Kidney Failure 5 <15 Kidney Failure

4. In this K/DOQI staging, “kidney damage” means: Persistent proteinuriaPersistent proteinuria Persistent glomerular hematuriaPersistent glomerular hematuria Structural abnormality:Structural abnormality: – such as PCKD, reflux nephropathy

5. CHRONIC KIDNEY DISEASE Diagnosis: Acute vs. chronic: –Small kidneys on U/S or unenhanced imaging mean CKD –Diabetic CKD may still have normal sized kidneys

6. CHRONIC KIDNEY DISEASE Common causes of CKD: Diabetic nephropathy Vascular disease GN PKD

7. CHRONIC KIDNEY DISEASE Causes of CKD: Best to divide as proteinuric or non-proteinuric CKD Proteinuric is much more likely to have deterioration in GFR and higher cardiovascular morbidity and mortality

8. CHRONIC KIDNEY DISEASE Treatment Delay progression: Treat underlying disease i.e. good glucose control for DM BP control to 130/80, (the current target) ACEI or ARB has extra benefit for proteinuric CKD Lower protein diet…maybe

9. CHRONIC KIDNEY DISEASE Treatment of the consequences of decreased GFR: –PO4: decrease dietary intake PO4 binders such as CaCO3 –Hypocalcemia: CaCO3, 1,25 OH D3

10. CHRONIC KIDNEY DISEASE Treatment of the consequences of decreased GFR: –Anemia: Erythropoetin current target Hb 105- 115

11. CHRONIC KIDNEY DISEASE Uremic Complications: Major: –Pericarditis –Encephalopathy –Platelet dysfunction

12. ARF

13. Pre renal and ATN most common causes ( quoted at 70% of cases of ARF) DDx: –Pre Renal –Intra Renal –Post Renal

14. U Na U Osm Fe Na Pre-Renal ATN Urine: Pre-Renal vs. Renal Assessment of Function Fe Na = U/P Na U/P Cr X 100 > 500< 1% > 40 < 350> 2% < 20 Pigmented granular casts found in up to 70% of cases of ATN

15. Fe Urea Pre-Renal ATN Urine: Pre-Renal vs. Renal Assessment of Function Fe Urea = U/P Ur U/P Cr X 100 > 55 < 35 FeUrea might be useful to Dx pre renal ARF in those who received diuretics…but not all studies support its use.

16. ARF Investigations: –Pre Renal: Urine tests as noted and responds to volume –Intra-Renal: look for GN, interstitial nephritis as well as ATN –Post Renal: Imaging showing bilateral hydronephrosis is highly specific for obstruction causing ARF

17. If cannot control these by other means: Hyperkalemia Pulmonary edema Acidosis Uremia (GFR < 10-15% for CRF) Dialysis: Who Needs It?

18. Hemodialysis is also used for intoxications with: –ASA –Li –Alcohols: i.e. methanol, ethylene glycol –Sometimes theophylline Dialysis: Who Needs It?

19. Na +

20. Hyponatremia Pseudo: –If total osmolality is high: hyperglycemia/ mannitol –If total osmolality is normal, could be due to very high serum lipoprotein or protein

21. Hyponatremia Volume status: –Hypovolemic: high ADH despite low plasma osmolality –High total volume: CHF/ cirrhosis have decreased effective circulating volume and high ADH despite low plasma osmolality

22. Hyponatremia Volume status: –If volume status appears normal: If urine osmolality is low: normal response to too much water intake…”psychogenic polydipsia” If urine osmolality is high: inappropriate ADH

23. Hyponatremia Treatment: –Hypovolemic: Replace volume –Decreased effective volume: Improve cardiac output if possible Water restrict –SIADH: Water restrict

24. Hyponatremia Treatment: –Rate of correction of Na: Not more than 10 mmol in first 24 h and not more than 18 mmol over first 48 h of treatment Or Central Pontine Myelinosis may occur

25. Potassium

26. Hyperkalemia Real or Not: –Hemolysis of sample –Very high WBC, PLT –Prolonged tourniquet time

27. Hyperkalemia Shift of K from cells: –Insulin lack –High plasma osmolality –Acidosis –Beta blockers in massive doses

28. Hyperkalemia Increased total body K: –Decreased GFR plus: High diet K KCl supplements ACEI/ARB K sparing diuretics –Decreased Tubular K secretion

29. TTKG Requirements: –Urine osmolality > 300 –Urine Na+ > 25 –Reasonable GFR TTKG = [urine K +  (urine osmol/serum osmol)] serum K + <7, esp < 5 = hypoaldosteronism U/P K + /U/P Osm

30. Hyperkalemia Treatment –IV Ca –Temporarily shift K into cells: Insulin and glucose Beta 2 agonists (not as reliable as insulin) HCO3 if acidosis present –Remove K

31. GFR

32. ASSESSMENT OF GFR:

33. (140-age) x Kg x1.2 Creat (x.85 for women) ASSESSMENT OF GFR: Cockroft-Gault estimated Creatinine clearanceCockroft-Gault estimated Creatinine clearance UCr x V PCr Need a Steady State for these to be valid Creatinine clearance formula:

34. Labs now calculate this for anyone who has a serum creatinine checked Use serum creatinine, age, gender Labs now calculate this for anyone who has a serum creatinine checked Use serum creatinine, age, gender MDRD eGFR

35. GFR, in mL/min per 1.73 m2 = (170 x (PCr [mg/dL])exp[-0.999]) x (Age exp[-0.176]) x ((Surea [mg/dL])exp[-0.170]) x ((Albumin [g/dL])exp[+0.318]) where SUrea is the serum urea nitrogen concentration; and exp is the exponential. The value obtained must be multiplied by 0.762 if the patient is female or by 1.180 if the patient is black. GFR, in mL/min per 1.73 m2 = (170 x (PCr [mg/dL])exp[-0.999]) x (Age exp[-0.176]) x ((Surea [mg/dL])exp[-0.170]) x ((Albumin [g/dL])exp[+0.318]) where SUrea is the serum urea nitrogen concentration; and exp is the exponential. The value obtained must be multiplied by 0.762 if the patient is female or by 1.180 if the patient is black. Simplified: GFR, in mL/min per 1.73 m2 = 186.3 x ((serum creatinine) exp[-1.154]) x (Age exp[-0.203]) x (0.742 if female) x (1.21 if African American) Simplified: GFR, in mL/min per 1.73 m2 = 186.3 x ((serum creatinine) exp[-1.154]) x (Age exp[-0.203]) x (0.742 if female) x (1.21 if African American) MDRD eGFR Do NOT memorize this formula

36. Limitations of GFR estimates: Not reliable for: extremes of weight or different body composition such as post amputation, paraplegiaextremes of weight or different body composition such as post amputation, paraplegia acute changes in GFRacute changes in GFR use in pregnancyuse in pregnancy eGFR greater than 60ml/min/1.73m 2eGFR greater than 60ml/min/1.73m 2

37. Proteinuria

38. Albumin vs. other protein –Dipstick tests albumin

39. PROTEINURIA Quantitative: –24 hour collection –ACR: random albumin to creatinine ratio –PCR: random protein to creatinine ratio

40. PROTEINURIA Microalbuminuria: less than dipstick albumin Can use albumin to creatinine ratio on random urine sample… best done with morning urine sample

41. Random Urine 24h Urine Random Urine 24h Urine ACR(g/mol)Albumin(mg/24h)PCR(g/mol)Protein(mg/24h) NormalMF<2.0<2.8<30<20<200 Micro- albuminuria MF2.0-302.8-3030-300 Macro- albuminuria >30>300

42. Nephrotic Syndrome Definition: –> 3 g proteinuria per day –Edema –Hypoalbuminemia –Hyperlipidemia and lipiduria are also usually present

43. Nephrotic Syndrome Causes: –Secondary: DM, lupus –Primary: Minimal change disease FSGS Membranous nephropathy

44. Nephrotic Syndrome Complications: –Edema –Hyperlipidemia –Thrombosis…with membranous GN and very low serum albumin

45. Nephrotic Syndrome Treatment: –Treat cause if possible –Treat edema, lipids –Try to decrease proteinuria

46. Hematuria

47. Significance: ≥ 3 RBC's per hpf DDx: Is it glomerular or not? Glomerular: –RBC casts –Dysmorphic RBCs in urine –Coinciding albuminuria may indicate glomerular disease

48. Hematuria Other investigation: –Imaging of kidneys –Serum creatinine –Age over 40-50 rule out urologic bleeding, i.e. referral for cystoscopy

49. Hematuria For glomerular hematuria without proteinuria DDx includes: –IgA nephropathy –Thin GBM disease –Hereditary nephritis

50. Ca ++, PO 4, Mg ++

51. Ca ++ and PO 4 -- Decreased GFR and increased PO4 Decreased Ca  1 OH of 25-OHD3 Increased PTH Renal osteodystrophy

52. Magnesium Hypomagnesemia: –GI loss/lack of dietary Mg –Renal loss: Diuretics Toxins esp cisplatin

53. Hypophosphatemia Shift Decreased total body PO 4 –GI loss/decreased intake –Renal loss Fanconi Syndrome? –Very rare renal tubular loss of: PO 4, amino acids, glucose, HCO 3 -

54. Acid-Base Approach to: –Resp or metabolic –Compensated or not –If metabolic: anion gap or not –Anion gap = Na - (Cl + HCO3)

55. Acid-Base “MUDPILES”: –Methanol –Uremia –Diabetic/alcoholic ketosis –Paraldehyde –Isopropyl alcohol –Lactic acid –Ethylene glycol –Salicylate Increased anion Gap acidosis:

56. Acid-Base Metabolic acidosis with normal serum anion gap can be due to: 1) GI losses of HCO3 2) Renal tubular acidosis

57. Acid-Base Hopefully will not need this. Normal renal response to acidosis is to increase ammoniagenesis and more NH4 will be found in the urine The “urine anion gap” is a way to estimate urinary NH4 Urine anion gap = urine (Na + + K + – Cl - ) If positive there is decreased NH 4 + production